JPH0368503A - Liquid medicine for contact lens - Google Patents

Abstract

PURPOSE:To obtain the subject liquid medicine almost free from affinity to hard and soft contact lens having a high oxygen permeability, free from adsorption on the lens and deposition on the lens and having a sufficient rotproof effect by admixing a glycine type ampholytic surfactant with a nonionic surfactant. CONSTITUTION:With a glycine type ampholytic surfactant having a high germicidal action against Pseudomonas aeruginosa, fungi and general bacteria, a suitable amount of a nonionic surfactant is admixed to obtain the objective liquid medicine for contact lens capable of preventing generation of slight turbidity due to the glycine type ampholytic surfactant, capable of preventing adsorption thereof on the contact lens, free from stimulation to the eyes, having a high stability and excellent in rotproof effect. The obtained liquid medicine can be used as an eye drop for both of oxygen-permeable hard and soft contact lens and also can be used as a germicidal preservative and a wash preservative.

Description

[Detailed Description of the Invention] (Background of the Invention) Contact lenses for vision correction were originally put into practical use as so-called hard contact lenses (hereinafter referred to as HCL) made of polymethyl methacrylate (hereinafter referred to as PMMA).
After that, polyhydroxyethyl methacrylate (hereinafter P
With the advent of water-containing soft contact lenses (hereinafter referred to as 5CL) made from HEMA, contact lenses have been broadly divided into hard and soft.

However, conventional ICLs made of PMMA have very little oxygen permeability, and therefore are uncomfortable to wear.
There are also concerns that overwear may cause eye damage, and that long-term use may have an effect on the corneal endothelium. Therefore, plastic materials with excellent oxygen permeability have been applied to contact lenses one after another, and hard contact lenses, which have dramatically improved oxygen permeability compared to conventional lenses, have appeared on the market.

These hard contact lenses are called oxygen-permeable hard contact lenses (GPHCL), and are mainly made of
Silicone acrylate polymers are made by copolymerizing cellulose acetate butyrate (CAB) or siloxaneyl alkyl methacrylate with PMMA, glycol dimethyl methacrylate, dimethyl itaconate, PHEMA, etc. in appropriate ratios, and fluoromethacrylate and mainly PMMA or siloxane. It is made of fluorosilicone acrylate copolymerized with rualkyl methacrylate.

These GPHCLs are different from conventional HCLs made of PMMA.
The oxygen permeability was significantly improved and the original objective was achieved, but the drawbacks are that the lens material is generally fragile and easily scratched by external physical forces, and that it has poor affinity with biological components and chemicals. expensive. Therefore, it is easily soiled and easily affected by drugs.

On the other hand, in SCL consisting only of PHEMA, like HCL,
Oxygen permeability is low and there is an overwear problem.
Recently, it has also become possible to wear it continuously'<< PHEM
A with mainly N-vinylpyrrolidone added, or P
MMA with N-vinylpyrrolidone and glyceryl methacrylate added, as well as non-hydrous SCL whose main components are butyl acrylate and butyl methacrylate.
While material development progressed, improvements were made to the thickness and water content of lenses, and SCL with increased oxygen permeability was actually commercialized and released on the market. However, these SC
Like GPHCL, L is also fragile in terms of material, and PHEM
Compared to SCL consisting only of A, it is more susceptible to the effects of chemical substances such as chemical solutions.

(Problem to be solved) Regardless of whether it is HCL or SCL, eye disorders such as dryness, cloudiness, and foreign body sensation occur very often while wearing contact lenses. In order to replenish the amount of water and make the wearing process smooth before wearing,
There is a strong need for a usoting solution. On the other hand, with the development of new materials for GPHCL, as mentioned earlier, the lens has become easier to get dirty as a handling problem. Therefore, GPH
In order to safely handle CL over a long period of time, even more care must be taken in handling it after installation than with conventional HCL. In particular, for GPHCL, cleaning after wearing and overnight soaking are effective in removing stains during wearing, and a contact lens solution such as a cleaning solution or a storage solution specifically for GPHCL is required.

Furthermore, the eye drops and wetting solutions mentioned above
It is necessary to maintain sterility not only before opening, but also for a long period of time after opening. However, due to the intended use of these liquid preparations, there is a high probability of bacterial contamination from fingers and eye mucous membranes, and therefore it is necessary to add a preservative to suppress and kill bacterial proliferation. Furthermore, since dirty lenses are immersed in the solution for a long period of time, it is necessary to add a preservative to the storage solution.

Conventionally, these contact lens solutions contain preservatives such as cationic surfactants such as benzalkonium chloride (BAK) and benzethonium chloride, chlorhexidine gluconate (GCH), chlorobutanol, para-aminobenzoic acid ester, and sorbic acid. and thimerosal have been used alone or in appropriate combinations.

However, cationic surfactants, GCH, and para-amino-7 benzoate have a very high affinity with GPHCL and SCL, and if eye drops, contact lens cleaning agents, or storage solutions containing these are used, , these preservatives are adsorbed and accumulated on the lens.

Furthermore, wearing contact lenses with a build-up of these preservatives greatly increases the possibility of eye damage. In addition, in GPHCL, lens cloudiness occurs due to cracks on the lens surface due to adsorption and accumulation of preservatives, and swelling of the lens causes drastic changes in the size, base curve, power, and center thickness of contact lenses. Changes may occur, which may lead to physical eye damage. Furthermore, boiling sterilization is mandatory for SCL in Japan, but if the preservative adsorbed on SCL is boiled and sterilized without being removed, the preservative will denature and stick on the surface and inside of SCL. However, such harmful components gradually accumulate in a situation where they cannot be easily eluted from the lens.

Looking at SCL drugs in the US (Nonprescript
ionDrugs 8th edition), contact lens solutions used during boiling sterilization do not contain cationic surfactants or G Cf as preservatives, and chlorhexidine gluconate is mostly used for cold sterilization. This is because of the following reasons.In addition, thimerosal and sorbic acid are used for severe punishment during boiling sterilization in the United States.However, thimerosal is difficult to use in Japan due to problems of accumulation in the human body and environmental pollution. The latter is
It inherently has weak preservative power and cannot guarantee the sufficient preservative effect that a contact lens solution should have.

As described above, among the preservatives conventionally used in contact lens solutions, there was no preservative that could be used in the recently developed hard and soft contact lenses with high oxygen permeability.

(Means for Solving the Problem) As a result of repeated studies on preservatives that can be used in contact lens solutions, the present inventors found that hard and soft contact lenses with high oxygen permeability compared to conventional preservatives. We have discovered that glycine-type amphoteric surfactants are extremely excellent as they have almost no affinity for lenses, therefore do not adsorb or accumulate on lenses, and can provide sufficient preservative power. Glycine type amphoteric surfactants are usually used as hydrochloride salts and are represented by the following general formula: [R'-(NHCII2CHf)t-N11C11
,C00I+]・llCl ・・・・・・・■[(R
'NHCl1. CI+, ), NCH, C0OH]・l
lCl ・・・・・・■ [In the formula, R1 is C8~
CI8 alkyl group, R1 represents a C8 alkyl group].

One of the glycine-type amphoteric surfactants is commercially available under the trade name TEGO [F], and TEGO-51° is the product listed above.
It has the structure of the formula, and R1 is an alkyl group of C, H, .about.C1,H3°. Furthermore, a commercially available product called TEGO-103° has the structure of the above formula (2).

These glycine-type amphoteric surfactants have a strong bactericidal effect against Pseudomonas aeruginosa, fungi, and general bacteria, and
It is also widely used in the medical field, including sterilizing instruments and operating rooms, bath preparations, athlete's foot treatments, and disinfecting surgical fields.

Glycine type amphoteric surfactants are 0.001-01% (w
/v%; all percentages shown below are w/v%). However, when aqueous solutions of various concentrations are prepared without adding a buffer or isotonic agent, the concentration is constant. A slight turbidity is observed in the appearance regarding the wave dissipation in the concentration range of . TEGO
The results observed using -51o are shown in Table 1 below.

Table 1. TEGO-51" water-soluble i&l:+ propertiesFor contact lens additives, clarity is an essential condition, and the above phenomenon cannot be tolerated.The actual cause of this slight turbidity is not clear, but In order to prevent the slight turbidity that occurs in a certain 4W area, the present inventors
As a result of examining various additives, we found that by adding an appropriate amount of nonionic surfactant, we were able to prevent this slight clouding and, as will be explained later, to improve the adsorption of glycine-type amphoteric surfactant onto contact lenses. was found to suppress Examples of nonionic surfactants include polyoxyethylene sorbitan fatty acid ester (TO-
100) Polyoxyethylene alkyl phenyl ether (e.g. 0
P-10o), polyoxyethylene alkyl ester (e.g. MYS-4
0 ■), polyoxyethylene alkyl ether (e.g. BL-9E
X■), polyoxyethylene hydrogenated castor oil (HCO-60”), etc.These nonionic surfactants are listed in the Japanese Pharmacopoeia, the official standards for cosmetic raw materials, etc., and are available as injections and It is widely used as an additive in medicinal cosmetics.

Table 2 shows the results of adding the above-mentioned nonionic surfactant at a concentration range that causes turbidity in TEGO-51o and observing the appearance.

0P-1ρ: Polyoxyethylene (10) octylphenyl ether MYS-40@): Polyoxyethylene (
40) Monostearate BL-9Ex@: polyoxyethylene (9> lauryl ether HCO-6ρ: polyoxyethylene (60) hydrogenated castor oil or more, if any nonionic surfactant is blended at 0.001% or more, Can prevent turbidity.

In addition, the blending concentration of nonionic surfactant is 0°001%.
However, in order to keep the contact lens solution clear for a long period of time and to suppress the adsorption of the glycine-type amphoteric surfactant to the contact lens, eye drops must have a 0. 0.01% to 0.5%, and 0.01% for other contact lens solutions.
A range of 2.5% is desirable.

In the contact lens solution of the present invention, inorganic salts such as sodium chloride, potassium chloride, sodium hydrogen phosphate, boric acid, borax, and citric acid can be used as pH adjusters, tonicity agents, and buffering agents. Further, as a stabilizer, ethylenediaminetetraacetate (eg, sodium salt) and a binder such as polyvinyl alcohol, polyvinylpyrrolidone, or hydroxyethylcellulose can be added.

In manufacturing the liquid preparation of the present invention, no special method is required, and in the same way as when making a normal aqueous solution, each component is dissolved using a predetermined amount of sterile purified water, and a clear aqueous solution is obtained. , sterile filtration, and sterile filling.

Next, specific preparation examples of the present invention and examples in which the effects on various contact lenses were compared with other preservatives will be shown. In the following studies, TEGO51o was used as the glycine type amphoteric surfactant, but it goes without saying that similar effects can be obtained by using other glycine type amphoteric surfactants. The contact lenses listed below were commercially available and unused.

G P HCL A (10 types) B PMMA K (1 type) Low water content 5CLL (1 type) Low water content SCL M (8 types) N High water content 5CLU (2 types) ■ Example I TEGO-51o and non-water content After dissolving the required amount of ionic surfactant together with inorganic salts in sterile purified water, it is aseptically filtered to obtain a sample solution. The inorganic salts used in the sample solution include sodium chloride, potassium chloride, sodium dihydrogen phosphate, boric acid, and borax, and the pH after preparation should be 7.2 and the osmotic pressure should be 290 mo sm/kg. (hereinafter abbreviated as BUFFER).

GPHCL (8 types) was immersed in each sample solution and comparative solution 2+nl shown in Table 3 below, and incubated at 34°C for 2 hours. The amount of preservative adsorption was determined by quantifying the preservative concentration in the solution, and comparing it with a similarly operated solution without lenses to calculate the preservative content that decreased during incubation, which was taken as the amount of adsorption onto the lens.

Table 3 below shows the results.

In conventional PMMA lenses, almost no preservatives are adsorbed, but some GPI (CL) materials have a very high affinity for preservatives.TE
GO-51■ can be used only in BUFFER or without other preservatives (
Compared to BAK), adsorption to G P HCL was relatively small, and almost no adsorption was observed due to the inclusion of a nonionic surfactant.

Example 2 GPHCL (1 type) was immersed in 12 ml of the following sample solution and comparative solution iff, stored at 34°C for one month, and then the base curve, power, size, and center thickness of the lens were measured, and the appearance was examined. Observed. The method for preparing the sample solution is the same as in Example 1. The results are shown in Table 4 below.

In addition, the comparative solution containing chlorobutanol caused variations in the specifications in all GPHCLs examined.

In the sample solution containing TEGO-51o, no effect on the lens was observed at all.

Example 3 A non-water-containing soft contact lens (1 type) was immersed in a sample solution and a comparative solution 1, and incubated at 34°C for 2 hours, and then the preservative/RU in the solution was quantified. The adsorption amount was calculated in the same manner as in 1.

Preparation was carried out in the same manner as in Example 1. The results are shown in Table 5 below.

For PMMA lenses, the specifications were not affected by various preservatives, but for GPHCL, the specifications were greatly affected by the type of formulation. In particular, Lens C in Example 1, which had a relatively high affinity with preservatives, had fine scratches on its surface and became cloudy. As in Example 1, the sample solution containing TEGO-51■ was found to be less adsorbed than the comparative solution containing other preservatives.

Implementation VA+4 Low water content 5CL (1 type) was immersed in the following sample solution and comparative solution 5IIll, and after incubating at 25°C for 24 hours, the preservative concentration in the solution was determined.
The adsorption amount was calculated in the same manner as above. The sample solution was prepared in the same manner as in Example 1. The results are shown in Table 6 below.

TEGO-51[F] showed little adsorption to SCL even without the addition of a nonionic surfactant, and by adding a nonionic surfactant, almost no adsorption was observed. Furthermore, the addition of salts had no effect on adsorption inhibition.

Example 5 Low water content 5CL (7 types) and high water content 5CL (2 types) were immersed in the following sample solution 5IIll, and heated at 25°C.
After incubation for 24 hours, the preservative concentration in the solution was determined, and the adsorption amount was calculated in the same manner as in Example 1. The sample solution was prepared in the same manner as in Example i. The results are shown in Table 7 below.

Table 7゜Preservative absorption Wffi (?7] /% of a degree)
It also has the preservative power that eye drops should have.

Claims (7)

[Claims] (1) A contact lens solution containing a glycine-type amphoteric surfactant and a nonionic surfactant as essential components. (2) The liquid preparation according to claim (1), further comprising an inorganic salt and/or ethylenediaminetetraacetate. (3) The solution according to claim (1), which is an eye drop before and during contact lens wearing. (4) Claim (1) which is a sterilizing preservative for contact lenses
). (5) Claim (1) which is a cleaning preservative for contact lenses
). (6) Glycine type amphoteric surfactant is 0.001 to 0.1
The liquid preparation according to claim (1), which is blended in w/v%. (7) The liquid preparation according to claim (1), which contains the nonionic surfactant in a concentration range of 0.001 w/v% or more, preferably 0.05 w/v% or more and 0.5 w/v% or less.